European Congress of Endocrinology 2009
Istanbul, Turkey
25 April 2009 - 29 April 2009
European Society of Endocrinology
BRAFV600E mutation and timp-1 hyper-expression in classical variants of papillary thyroid carcinoma (PTC)
University of Palermo, Palermo, Italy.
BRAFV600E mutation is considered useful in recognizing thyroid cancer aggressiveness or poor prognosis particularly in certain variants of papillary thyroid cancinoma (PTC). A recent meta-analysis identified 12 cancer-versus-non cancer gene candidate as markers of thyroid cancer; among these TIMP-1 (tissue inhibitors of metalloproteinases) was found consistently up-regulated. Our aim was to evaluate BRAFV600E mutation and TIMP-1 expression in 14 PTC classical variants (CV) in comparison to 14 PTC other variants (2 tall-cell, 8 follicular, 4 sclerosant variants; OV). BRAFV600E mutation was detected in 11 (78.6%) CV-PTC and in 3 (21.4%) OV-PTC. Using qRT-PCR TIMP-1 was found significantly hyper-expressed in CV-PTC harbouring BRAFV600E mutation (median 14.3 (interquartile range: 8.2–40)) in comparison to respective normal tissues (1.2 (1–2.2); P=0.004). A significant TIMP-1 hyper-expression was confirmed in all 14 BRAF-mutated PTC (median 22.9 (9.2–89.3)) with respect to 14 wild type PTC (median 6.3 (2–13.8); P=0.024).
The proof-of-principle was assessed in vitro using BCPAP cell line, which harbours BRAFV600E mutation, and was found to hyper-express TIMP-1. When BCPAP cells were transiently transfected with target-specific BRAF-siRNA (MU-A) TIMP-1 was significantly down-regulated. Our data prove that BRAFV600E mutation is strongly associated with TIMP-1 up-regulation in CV-PTC, suggesting their potential invasiveness through the well-known TIMP-1 anti-apoptotic activity.
Endocrine Abstracts (2009) 20 P76